Cancer is the second leading cause of deaths in the USA, accounting for nearly one of every four deaths. It is estimated that in the USA there will be more than 1.6 million new cases of cancers with more than 535,000 deaths associated with cancer in 2014 alone. Existing treatments are limited by server side effects owing to non-specific drug actions on non-cancer cells. A recent concept in cancer therapy is that strong immune surveillance is capable of detecting and eliminating cancer cells. Research has shown that an active immune system is needed to clear tumors after chemotherapy with a commonly used anti-cancer drug, cisplatin. Ironically, cisplatin adversely affects the patient's immune system by killing white blood cells (WBC) and, importantly, solid tumors usually escape immune destruction by suppressing the anti-cancer immunity at the tumor site by creating a unique micro-environment through metabolic alterations. Furthermore, cisplatin treatment has the significant drawback of dose dependent side effects. The side effects of cisplatin chemotherapy include general cell damaging effects such as nausea and vomiting, bone marrow suppression and immunesuppression. More specifically, cisplatin causes acute kidney damage (nephrotoxicity) and hearing loss (ottotoxicity).
Many approaches have been tried to reduce cisplatin toxicity. Drug delivery approaches such as formulation of cisplatin containing liposomes, nanoparticles and complexes did not result in significant advantage and failed to receive any substantial clinical attention. Chemical modification approaches such as derivatising cisplatin and conjugating cisplatin to polymers have also been tried with limited success. These are complex procedures that may not suitable for clinical application. Accordingly, there is a need in the art to target cisplatin and other chemotherapeutic drugs to tumor cells to maximize efficacy while minimizing side effects.